With the sophistication of modern medical products, there has arisen a need to maintain such products while stored in narrow temperature ranges. Living organisms and cultures often must be maintained as near as possible to the "incubation point" (about 37.degree. Centigrade) during storage and shipping. Other drugs, hormones and vaccines must be stored and shipped as close as possible to the freezing point (0.degree. C.). However, these materials are damaged--and in some cases becoming fatally dangerous--if they are allowed to freeze. Insulin is a common example of such a hormone.
Ever since Banting and Best isolated insulin in 1922, diabetics the world over have become dependent upon this life giving hormone. A suspension of this polycrystalline material must be injected at least once daily for the typical Type 1 (juvenile onset) diabetic person to remain healthy. About one-half of the people with Type II (adult onset) diabetes also must take insulin. Often physicians will prescribe two different types of insulin to take with each injection, and also may require that several injections be taken each day. The diabetic can be in serious trouble without his insulin, and unless each insulin dose is carefully measured, hypoglycemia and sudden loss of consciousness may result.
Insulin is a temperature sensitive material. If it has been frozen, large particles, called clumps, permanently form in the injection vial. This clumping also takes place if the insulin suspension has been exposed to excessive temperatures.
The clumps will easily pass through the injection needles. However, a measured dose of this clumped material may contain many times the number of insulin crystals which otherwise would have been present in a similarly measured dose of unfrozen or unheated insulin. Since the biological potency of insulin is largely proportional to the number of crystals injected, life threatening errors in dosage can result from the use of clumped insulin.
Clumping will take place with crystal clear "Regular" insulin, without any noticeable change in appearance of the vial. However, the clumping effect is much more severe and potentially dangerous with the slower acting insulin preparations such as the isophane, zinc, and protamine suspensions commonly used by diabetics.
Another effect known as "fibril formation" takes place if insulin is exposed to room temperatures for any length of time. The new bio synthetic insulins are particularly prone to this effect.
Use of fibrilized insulin presents the same dangers as use of the clumped hormone. Also, the fibrils will clog the needles and orifices of syringes and jet injectors--a major problem with the new "insulin pens."
Apart from clumping and fibril formation is the degradation of insulin caused by exposure to light or by mechanical agitation and light. Just a few hours exposure to direct sunlight will result in substantial loss of potency. Indirect sunlight, for example, encountered when the vial is kept on a window sill, or in a room with florescent lighting, simply slows the rate of degradation. Shaking or vibration of the insulin vial results in similar loss of potency.
The ideal storage conditions are a temperature as close to freezing as practical, without actually freezing, and protection from mechanical agitation. The insulin manufacturers and their distributors try to maintain finished inventory while in storage or transit within the range of 2.degree.-8.degree. C. Only if stored within this temperature range, and protected from sunlight and mechanical agitation, can the manufacturer guarantee product quality to its expiration date.
Diabetes has afflicted mankind since time immemorial. However, in the past two decades its increase has exceeded the increase in world population by a considerable margin, brought about largely by the increase in longevity. A 1985 report by the World Health Organization states that seven percent of the population of the developed countries will have acquired diabetes by the age of forty. In the U.S. alone, it is estimated that there are over 10 million diabetics, about half of whom should take insulin.
Transport of such drugs is difficult. Simply stated, transport can only occur when it is assured that the drugs will be maintained as close as possible to their required temperature ranges. When this is understood, the inadequacy of conventional so-called "instrument quality" shipping devices can be understood.
First, one must understand that with respect to a drug that can only be stored in narrow temperature ranges, two things can happen. First, the drug can become too hot. Second, the drug can become too cold. Therefore, any system utilized during shipping must be capable of heating the shipment before it becomes too cold and cooling the shipment before it becomes too hot--all within the required narrow temperature ranges.
Conventional refrigeration and heating cycles are incompatible with most shipping requirements. The required apparatus and associated controls are too large--especially when relatively small quantities of temperature sensitive drugs must be rapidly shipped, as by air freight. One solution that has suggested itself is to use certain all electric heating and cooling equipment.
In such all electric heating and cooling equipment, resistance heating is utilized for adding thermal energy and so-called Peltier effect solid state heat pumps are utilized for cooling. Thus, the storage system can be simplified to essentially solid state electric devices and electric generation or battery devices having sufficient power to maintain the required temperature ranges during storage and/or transport.
The importance of absolute minimum power consumption can be further illustrated by considering the growing awareness and need for temperature control of medical materials in under developed countries and in remote locations where solar cell systems are the only practical source of electric power.
Unfortunately, the use of such temperature control devices has been curtailed by the lack of accurate, power conserving thermostats. A discussion of the inadequacy of conventional thermostats in the narrow temperature range environment is believed instructive.
The following discussion primarily concerns mechanical thermostat systems. Electronic temperature control systems using thermocouples, thermistors, and other electronic sensors together with associated circuitry, are either too large, too power consuming or too expensive for the applications considered here.
All conventional mechanical thermostats have two major control characteristics. One control characteristic is "differential" or hysteresis; this the difference between the devices "on to off" and "off to on" states. The other control characteristic is "tolerance"; this is the variation to which devices of the same class can be relied upon to change from one condition to the other. Remembering that utilizing conventional technology that a conventional thermostat is a single pole, single throw device, and that one device is required to control the heating apparatus and that another such device is required to control the cooling device, the inadequacies of these heating and cooling controls can be understood. Note, single pole, double throw devices will be discussed later.
Taking the case of relatively sensitive but inexpensive thermostats--which would be economically practicable with as shipping heating and cooling system--thermostats having a differential of no more than 5.6.degree. C. and a tolerance of 0.8.degree. C. can be reasonably purchased (currently for about $8.00). This will give a maximum temperature spread between the on and the off cycles of such devices of 7.2.degree. C.
Now let us suppose that two such devices are utilized, one for heating and the other for cooling. Further, and in order to avoid both heating and cooling devices being in the "on" state simultaneously we separate the supposed devices by a safety margin of just 0.6.degree. C.--a wholly impractical separation. It will be found that it will not be possible to control the temperature of the resulting heated and cooled shipment within a thermal range of less than 15.degree. C!
Unfortunately, another problem enters this rather difficult temperature control environment. Where the two heating and cooling devices are placed as close as possible in the operating ranges to maintain temperature control within narrow thermal limits, the possibility of both the heating and cooling devices being in the "on" state emerges. Assume that the controlled environment becomes too cool and the heater turns on. Further assume that as the temperature rises--but before the heater turns off, the cooler is turned on. A condition known as "thermal lockup" is created. Taking the case of an all electric heating and cooling system relying on a finite and concomitantly shipped power source--such as a battery--required temperature control energy will be rapidly used. If all energy is consumed before the shipped goods reach their required destination, spoilage may result.
Because of the possibility of the condition known as thermal lockup, such individual heating and cooling thermostats are not set as closely in their respective operating ranges as might be desired for the required temperature control. The result is even further temperature excursion of the stored and/or shipped drugs.
Precision single pole double throw (SPDT) "snap action" mechanical thermostats are available from manufacturers. However, thermostats of this type suffer from the problems of differential and tolerance previously described and are thus unsuitable where narrow temperature control ranges are necessary. Although these SPDT thermostats can be used to eliminate the thermal lockup condition, they present another problem--the SPDT element instantaneously switches from one contact to the other. Thus, heating or cooling is always on, even when the shipment is within its desired temperature range and neither heating or cooling is required. This can be as wasteful of power as the thermal lockup condition.
As stated earlier, an ideal temperature range for storing and shipping insulin, certain hormones, vaccines, and other drugs is 2-8.degree. C. In incubation application applications, a temperature range of 35-37.degree. C. is often required. As has been shown, these narrow control ranges are not practical with conventional miniature mechanical thermostat systems, and sophisticated electronic systems needed for such tight temperature control are either too large, too power consuming, or too expensive for the application.
For purposes of saving power, neither heating or cooling should be applied, or remain on, so long as the shipment is within its acceptable temperature range. For example, when the desired temperature range is from 2.degree. to 8.degree. C., an ideal situation would have the temperature spread between application of heating or application of cooling ("dwell") as wide as practical, but never exceeding 6.degree. C. Similarly, in the incubation application, the dwell should be as close to 2.degree. C. as practical but never exceeding 2.degree. C.
Assuming that temperature control is required for drug goods in transport--such as during conventional "air freight" or the conventional air plane travel of a diabetic--other problems immediately surface. Vibration is such a problem. Typically, the shipper or traveller has no control over such vibration; any temperature control system must consequently be reasonably resistance to vibration.
Simply stated, temperature control within narrow operating ranges is other than trivial--especially where storage during transport is required.
Consequently, there is a need for a temperature control device which can be used during storage and transport for the control of heating and cooling devices to maintain temperatures sensitive materials within narrowly defined temperature ranges while consuming a minimum amount of power. This disclosure is directed to such a device.